Protein kinase c

Protein kinase C plays a central role in signal transduction. Its activity is controlled by hormones and neurotransmitters , whose signal is transmitted via secondary messengers. Protein kinase C is subject to a complex activation sequence before it becomes completely catalytically active. Calcium ions (Ca2+), phospholipids and diacylglycerol are necessary for its activation. Sphingosine on the other hand inhibits protein kinase C.

Protein kinase C is of fundamental importance in the regulation of cellular growth. A misregulation of protein kinase C can be involved in the induction of malignant tumours and in the development of diabetic late complications.

Mutations of protein kinase C have been detected in Kawasaki syndrome.

Protein kinase C and diabetes: In patients with diabetes mellitus, elevated blood glucose levels lead to an increase in the diacylglycerol concentration (DAG) in the cell and thus to an activation of protein kinase C. This promotes the production of extracellular matrix and cytokines, increases the contractility and permeability of blood vessels, increases cell growth in blood vessels, activates phospholipase A2 and inhibits Na+/K+-ATPase. As a result, the retina of the eye, kidney and heart are damaged.

Ten isoenzymes of protein kinase C are currently known. Three groups of PKC isoenzymes can be distinguished:

• the classical PKC (cPKC) - cPKC isoforms: α, β1, β2, γ isoforms
• the new PKC (nPKC) - nPKC isoforms: ε, δ, η and θ Isoforms
• the atypical PKC (aPKC) - aPKC isoforms: ζ and λ/τ.

Furthermore, a PKCμ is known, which is however referred to as protein kinase D1. The molecular masses of the different PKC isoforms range from 61 to 154 kDa.

The importance of protein kinase C for cell division and proliferation was clearly demonstrated by analysis of the mode of action of different proteins. phorbol esters. Phorbol esters are polycyclic alcohol derivatives and potent carcinogens such as TPA (12-tetradecanoyl phorbol 13-acetate). Phorbol esters do not themselves initiate tumour formation. However, they promote the effect of carcinogenic substances. The esters activate protein kinase C due to their similarity to the natural activator DAG (diacetylglycerol). The activity thus mediated persists for a long time, since phorbol esters, in contrast to DAG, are degraded only very slowly.